(EN) Obesity and type 2 diabetes mellitus (T2DM) are among metabolic disease with increasing incidence and prevalence. Last decade has been devoted to intensive research focused on pathophysiological mechanisms underlying development of these diseases. Besides environmental factors, lifestyle and amount and composition of food, adipose tissue is a key player in the pathogenesis of obesity and its metabolic complications including insulin resistance (IR) and T2DM. Primary aim of our work was to evaluate the role of recently discovered adipokine omentin and the role of mitochondrial dysfunction in subcutaneous adipose tissue (SCAT) and in peripheral monocytes (PM) in patients with obesity and T2DM with respect to the development of insulin resistance and diabetes. A total number of 118 subjects enrolled in the study were divided into three groups: patients with obesity and T2DM (T2DM group), obese non-diabetics (OB) and healthy lean subjects as a control group (KO). Study subjects underwent several types of interventions - 2 to 3 weeks of very-low calorie diet (VLCD, energy intake 600 kcal per day), regular physical activity program or bariatric surgery (laparoscopic sleeve gastrectomy, LSG). Results indicate that low serum omentin concentrations may contribute to development of obesity-associated...

Aujourd’hui la restriction calorique modérée et chronique (RC) est la seule intervention non génétique capable de ralentir l’apparition de pathologies liées à l’âge et d’accroître la longévité chez plusieurs espèces animales. Le resvératrol (RSV), un composé appartenant au groupe des polyphénols, présente des propriétés thérapeutiques intéressantes et constitue un candidat prometteur comme mimétique des effets d’une RC. Afin d’évaluer l’impact de tels protocoles nutritionnels à long terme, une étude longitudinale a été menée sur une cohorte de 53 mâles microcèbes (Microcebus murinus), modèle primate pertinent pour les recherches sur le vieillissement normal ou pathologique au vue de sa longévité maximale de 12 ans en captivité. Depuis l’intégration des animaux dans l’étude (3 ans d’âge) à l’avancement actuel du projet (8 ans d’âge), des paramètres physiologiques et comportementaux ont été évalués régulièrement au sein de la cohorte, partagée en trois groupes: un groupe soumis à une RC (-30%) et un groupe supplémenté en RSV (200 mg.kg-1.jour-1), comparés à un groupe contrôle (CTL). Avec l’âge, chez les microcèbes CTL, des perturbations sont apparues : diminution de la sensibilité à l’insuline, accumulation de dommages cellulaires, déclin moteur et cognitif (mémoire spatiale de reférence) et déclin de certains marqueurs prédictifs du vieillissement chez cette espèce. La RC a permis une amélioration de la sensibilité à l’insuline et a limité l’accumulation de certains marqueurs du stress oxydant, elle n’a pas entraîné d’amélioration des capacités cognitives, mais a diminué l’anxiété, amélioré les performances motrices et augmenté l’activité locomotrice spontanée. La RC a aussi induit une réponse adaptative métabolique avec une perte de masse corporelle sans réduire les dépenses énergétiques, un abaissement des taux hormonaux d’IGF-1 et de la testostérone suggérant un compromis entre reproduction et survie. Le RSV a mimé une partie des effets bénéfiques démontrés sous RC. Cependant il a permis une amélioration de la mémoire spatiale de travail, absente chez les animaux restreints. Le RSV a également montré des effets opposés à ceux de la RC comme un maintien de la masse corporelle et des taux d’hormones par rapport aux CTL, une augmentation des dépenses énergétiques et des niveaux de testostérone pendant la période de jours longs. Finalement les données de survie actuelles sont prometteuses ; moins de 50% de l’effectif de départ des animaux CTL a survécu, alors que plus de 50% des animaux RC et RSV sont encore vivants, présentant de surcroît un âge moyen à la mort plus élevé d’environ 1 an par rapport aux CTL. Malgré des effets hétérogènes et pourtant bénéfiques, la RC et le RSV sont capables de ralentir l’apparition de certains déclins intrinsèques au vieillissement et d’améliorer la survie des microcèbes, soutenant l’hypothèse selon laquelle ces effets pourraient être induits par des mécanismes différents mais permettant d’atteindre les mêmes issues favorables notamment au niveau de l’espérance de vie. Ces résultats constituent un véritable outil pour la compréhension future des mécanismes sous-jacents au processus du vieillissement mais aussi des voies de régulation cellulaires mises en jeu par la RC et le RSV à moyen et long terme chez un primate / Nowadays moderate and chronic calorie restriction (CR); is the only non-genetic intervention known to slow the onset of age-related diseases and to increase longevity in several animal species. Resveratrol (RSV), a natural compound belonging to the polyphenols group, has therapeutic properties and is a promising candidate as CR effects mimetic. To assess the impact of such long-term nutritional protocols, a longitudinal study was conducted on a cohort of 53 males grey mouse lemurs (Microcebus murinus), a relevant primate model for normal and pathological aging research as regards to its high longevity in captivity, up to 12 years. Since the integration of the animals in the study (3 years old) to the current status of the project (8 years of age), physiological and behavioral parameters were assessed regularly in the cohort divided into three groups: a group submitting to a -30% CR and a group supplemented with RSV (200 mg.kg-1.day-1), compared to a control group (CTL). With age, disturbances appeared in CTL mouse lemurs: decreased insulin sensitivity, accumulation of cellular damage, motor and cognitive decline associated with particular type of memory and a decline of certain predictive biomarkers of aging in this species. CR has improved insulin sensitivity and limited the accumulation of markers of oxidative stress, it has not resulted in improved cognitive abilities but in a decreased anxiety, improved motor performances and an increased spontaneous locomotor activity. CR also induced an adaptive metabolic response with body weight loss without lowering energy expenditure, lower hormone levels of IGF-1 and testosterone, supporting a probable trade-off between reproduction and survival. RSV mimicked some of the beneficial effects demonstrated in CR. However, it has improved the spatial memory task, which was not observed in restricted animals. RSV also showed opposite effects to those of CR, as maintained body weight and hormone levels compared to CTL, an increase in energy expenditure and in testosterone levels during the long day’s season. Finally, the current survival data are promising; less than 50% of the CTL animals survived, while more than 50% of CR and RSV animals are still alive, with in addition a mean age at death about 1 year higher compared with CTL animals. Despite heterogeneous, but yet beneficial effects, CR and RSV were able to slow the appearance of some intrinsic age-related declines and to improve the lemurs’ survival, supporting the hypothesis that these effects may be mediated by different mechanisms achieving the same positive outcomes including enhanced life expectancy. These evidences are a real tool for the future understanding of the mechanisms underlying the aging process but also of cellular regulatory pathways that are involved in long term CR and RSV treatment in a primate

Les labels présents sur les emballages (e.g., « bio », « commerce équitable ») peuvent pousser les individus à sous-évaluer le contenu calorique des aliments, créant ainsi un effet de halo santé. Dans cette thèse, nous défendons l’idée qu’un mécanisme de fausse attribution affective pourrait en partie expliquer cet effet de halo santé. Nous présenterons 11 études ayant pour but de tester empiriquement cette hypothèse. Parmi les principaux résultats, nous avons montré qu’il était possible d’observer cet effet même si les individus ne rapportent pas avoir pris en compte le label dans leur évaluation (Etudes 3) et dans un contexte de double tâche entravant un raisonnement délibéré de leur part (Etudes 4 et 5). Nous avons également pu montrer, par le biais d’une tâche de fausse attribution affective, qu’un stimulus neutre, lorsqu’il est précédé d’un label bio (vs. une image contrôle) est ensuite évalué plus positivement (Etudes 6, 7 et 8). Enfin, nous avons observé une congruence systématique entre la valence de l’amorce (i.e., le label) et la valence de l’évaluation subséquente d’un stimulus neutre (i.e., le contenu calorique d’un produit alimentaire ; Etudes 9, 10 et 11). Ce biais cognitif relatif à nos évaluations caloriques apparaît donc comme un phénomène robuste, ne faisant intervenir que peu d’inférences délibérées de la part des individus et étant guidé par la valence du label (qu’il soit positif ou négatif). / Labels on food products can lead to unwarranted inferences: organic and fair-trade products are perceived as containing fewer calories. This effect is described in the literature as the health halo effect. In this thesis, we argue that an affective misattribution mechanism can partially explain this effect. We present 11 studies testing empirically this hypothesis.Among our main results, we show that this effect still occurs even if participants did not mention that they used the label in their evaluation (Study 3) and when they are under cognitive load, hindering a deliberate reasoning (Studies 4 and 5). By using an affective misattribution procedure, we also show that when a neutral stimulus is preceded by an organic label (vs. a control picture), this stimulus is then evaluated more positively (Studies 6, 7, and 8). Finally, we observed a systematic congruency between the valence of the prime (i.e., the label) and the valence of the evaluation of a neutral stimulus (i.e., the caloric content of a food product; Studies 9, 10, and 11). Taken together, these studies suggest that this cognitive bias is a robust phenomenon, involving a few inferences and mainly driven by the valence of the label (whether positive or negative).

The prevention and treatment of obesity is a major problem of health care systems in affluent societies. Metabolism of adipose tissue belongs to the therapeutical targets, since accumulation of adipose tissue is the basis of obesity development. Experiments using transgenic mice with ectopic expression of brown- fat uncoupling protein 1 (UCP1) in white adipose tissue (WAT), verified a concept that obesity could be ameliorated by increasing energy expenditure in WAT. The goal of the experiments of this PhD Thesis was to characterize in detail the phenotype of this unique animal model of obesity resistance. We have shown that mitochondrial uncoupling in WAT resulted in increased oxidation of fatty acids (FA), in face of decreased lipogenesis and induced mitochondrial biogenesis in this tissue. In further studies, we aimed to modulate propensity to obesity be increasing FA oxidation in WAT in response to physiological stimuli. This could be accomplished in response to the combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) and mild calorie restriction in mice fed high-fat diet. Synergistic induction of mitochondrial oxidative capacity and lipid catabolism in epididymal WAT was associated with suppression of low-grade inflammation of WAT, which is typical for obesity. The improvement of lipid...

In order to decrease our dependence on non-renewable petrochemical resources, it is urgently required to establish sustainable biomass-based biorefineries. Replacing fossil fuels with renewable biomass as a raw feedstock for the production of chemicals and biofuels is a main driving force of biorefinering. Almost all kinds of biomass can be converted to biochemicals, biomaterials and biofuels via continuing advances on conversion technologies. In vitro synthetic biology is an emergent biomanufacturing platform that circumvents cellular constraints so that it can implement some biotransformations better than whole-cell fermentation, which spends a fraction of energy and carbon sources for cellular duplication and side-product formation. In this work, the in vitro synthetic (enzymatic) biosystem is used to produce a future carbon-neutral transportation fuel, hydrogen, and two high-value chemicals, a sugar phosphate and a highly marketable sweetener, representing a new portfolio for new biorefineries. Hydrogen gas is a promising future energy carrier as a transportation fuel, offering a high energy conversion efficiency via fuel cells, nearly zero pollutants produced to end users, and high mass-specific and volumetric energy densities compared to rechargeable batteries. Distributed production of cost-competitive green hydrogen from renewable biomass will be vital to the hydrogen economy. Substrate costs contribute to a major portion of the production cost for low-value bulk biocommodities, such as hydrogen. The reconstitution of 17 thermophilic enzymes enabled to construct an artificial enzymatic pathway converting all glucose units of starch, regardless of the branched and linear contents, to hydrogen gas at a theoretic yield (i.e., 12 H2 per glucose), three times of the theoretical yield from dark microbial fermentation. Using a biomimetic electron transport chain, a maximum volumetric productivity was increased by more than 200-fold to 90.2 mmol of H2/L/h at a high starch concentration from the original study in 2007. In order to promote economics of biorefineries, the production of a sugar phosphate and a fourth-generation sweetener is under development. D-xylulose 5-phosphate (Xu5P), which cannot be prepared efficiently by regular fermentation due to the negatively charged and hydrophilic phosphate groups, was synthesized from D-xylose and polyphosphate via a minimized two-enzyme system using a promiscuous activity of xylulose kinase. Under the optimized condition, 32 mM Xu5P was produced from 50 mM xylose and polyphosphate, achieving a 64% conversion yield, after 36 h at 45 °C. L-arabinose, a FDA-approved zero-calorie sweetener, was produced from D-xylose via a novel enzymatic pathway consisting of xylose isomerase, L-arabinose isomerase and xylulose 4-epimerase (Xu4E). Promiscuous activity of Xu4E, a monosaccharide C4-epimerase, was discovered for the first time. Directed evolution of Xu4E enabled to increase the catalytic function of C4-epimerization on D-xylulose as a substrate by more than 29-fold from the wild-type enzyme. Together, these results demonstrate that the in vitro synthetic biosystem as a feasible biomanufacturing platform has great engineering, and can be used to convert renewable biomass resources to a spectrum of marketable products and renewable energy. As future efforts are addressed to overcome remaining challenges, for example, decreasing enzyme production costs, prolonging enzyme lifetime, engineering biomimetic coenzymes to replace natural coenzymes, and so on. This in vitro synthetic biology platform would become a cornerstone technology for biorefinery industries and advanced biomanufacturing (Biomanufacturing 4.0). / Ph. D.

Indiana University-Purdue University Indianapolis (IUPUI) / The study was conducted to examine the communication between the customer and the cashier at the point of purchase in the process of determining the impact of the labeling laws. This study used an inductive qualitative design for data collection and data analysis. Data from this study suggest that calorie counts on menu labels are discussed frequently between the customer and the cashier at the point of sale at fast-casual restaurants. The data found gives us a framework and rationale as to why previous research on the effectiveness of the calorie labeling law in the Affordable Care Act have yet to make a significant impact in reducing consumer’s total daily caloric intake when eating food away from the home and found three specific reasons as to why the calorie labeling law may not be working the way the government intended it to. First, consumers at fast-casual restaurants rely on the cashiers as calorie guides because they are not aware or knowledgeable about the recommended daily caloric intake and often underestimate the total calories in their meals. Secondly, the study’s findings indicate that when restaurants offer lower calorie choices and downsizing options like a “small pita” at Pita Pit instead of a “regular pita”, many consumers buy the downsized item or smaller portion but food chains are not downsizing their signature items. Third, the study examined if the cashiers are trained in any way to discuss new regulations and calorie count/nutritional value and not one cashier was trained specifically about the calorie labeling law and why certain foods on the menu have more calories than others even though they are influencing decision making. Conversations at the point of sale have been routinely ignored in research about the calorie labeling law and this research helps to understand the choices consumers are making with the newly implemented calorie labeling regulation. The results from this study helps us further advance our understanding as to why consumers make the food choices they do while eating at restaurants.

Résumé : Les personnes atteintes de la maladie d’Alzheimer présentent une diminution de la capture cérébrale du glucose, qui semble être impliquée dans le développement des problèmes cognitifs associés à la maladie. Toutefois, il n’y a encore aucun consensus quant à savoir si la capture cérébrale du glucose est diminuée chez les personnes âgées cognitivement saines. En condition de déficit de glucose, les cétones sont le substrat énergétique alternatif pour le cerveau. La diète cétogène, induisant une cétose légère, améliore les fonctions cognitives chez les modèles animaux et chez l’homme. Notre premier objectif était d’évaluer l’effet du vieillissement sain et de la diète cétogène sur la capture cérébrale du glucose et des cétones chez le rat. Pour cela, la capture cérébrale de radiotraceurs analogues au glucose et aux cétones a été mesurée par tomographie par émission de positons. Nos résultats montrent que la capture des deux principaux substrats énergétiques du cerveau est globalement similaire chez des rats sains jeunes et âgés, mais est plus élevée suite à la diète cétogène. L’induction d’une cétose légère pourrait corriger la diminution de capture cérébrale du glucose subvenant au cours de la maladie d’Alzheimer. Le second objectif était de déterminer l’effet d’une diète cétogène sur le métabolisme cérébral du glucose et des cétones chez le rat. Pour cela, les différents intermédiaires des voies métaboliques du glucose et des cétones ont été mesurés par spectroscopie par résonance magnétique nucléaire. Les résultats démontrent que le métabolisme du glucose et des cétones dans les cellules du cerveau est plus élevé suite à la diète cétogène. Le contenu en acide [gamma]-aminobutyrique, le principal neurotransmetteur inhibiteur, est aussi plus élevé suite à la diète cétogène, ce qui pourrait contribuer à l’effet antiépileptique de la diète cétogène. Le troisième objectif était d’évaluer l’impact d’une restriction calorique à long terme, pouvant induire une cétose légère, sur le métabolisme cérébral chez des rats âgés sains. Nos résultats montrent que, couplée à une diète à haute teneur en sucrose et faible en acides gras oméga-3, la restriction calorique à long terme chez les rats âgés ne modifie pas le profil des métabolites et des acides gras du cerveau. La déficience en acides gras oméga-3 et la surcharge de sucrose pourraient empêcher une grande partie des effets bénéfiques de la restriction calorique au cerveau.//Abstract : Alzheimer’s disease is associated with a reduction of brain glucose uptake, which may be involved in the development of the cognitive problems associated with the disease. It is however unclear whether brain glucose uptake is decreased in the cognitively healthy elderly. Under conditions of glucose deficit, ketones are the alternative brain energy substrate. A mild ketosis, induced by the ketogenic diet, improves cognitive functions in animal models and humans. Our first objective was to evaluate the effect of healthy aging and of a ketogenic diet on brain glucose and ketone uptake in the rat. Brain uptake of radiotracers analogous to glucose and ketones was measured by positron emission tomography. Our results show that the uptake of the brains two main energy substrates is generally similar in healthy young and aged rats, but is higher under the ketogenic diet. The induction of a mild ketosis may compensate the reduction of brain glucose uptake occurring in Alzheimer’s disease. The second objective was to assess the effect of a ketogenic diet on brain glucose and ketone metabolism in the rat. Metabolic pathway intermediates of glucose and ketones were measured by nuclear magnetic resonance spectroscopy. Results show that glucose and ketone metabolism in brain cells is higher under the ketogenic diet. Content of [gamma]-aminobutyric acid, the main inhibitory neurotransmitter, is also higher under the ketogenic diet, which could contribute to the antiepileptic effect of the ketogenic diet. The third objective was to evaluate the effect of a long-term calorie restriction, which may induce a mild ketosis, on brain metabolism in healthy aged rats. Our results show that, in conjunction with a diet enriched in sucrose and low in omega-3 fatty acids, long-term calorie restriction in aged rats does not change brain metabolite and fatty acid profiles. Omega-3 fatty acid deficiency and an overload of sucrose may prevent the beneficial effects associated with calorie restriction in the brain.

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-28T12:43:48Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇÃO MONIQUE BABINSKI_Pós Defesa 2016 SEM APENDICES (1).pdf: 1899605 bytes, checksum: 5667910f275aadea7cc77dcc4a1ea0c1 (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-28T12:44:09Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇÃO MONIQUE BABINSKI_Pós Defesa 2016 SEM APENDICES (1).pdf: 1899605 bytes, checksum: 5667910f275aadea7cc77dcc4a1ea0c1 (MD5) / Made available in DSpace on 2017-09-28T12:44:09Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇÃO MONIQUE BABINSKI_Pós Defesa 2016 SEM APENDICES (1).pdf: 1899605 bytes, checksum: 5667910f275aadea7cc77dcc4a1ea0c1 (MD5) Previous issue date: 2016 / Complexo Hospitalar de Niterói / O objetivo deste estudo foi avaliar os efeitos da restrição proteica e calórica materna durante a lactação, analisando se haveria recuperação, o conhecido “catch-up” das dimensões morfológicas femorais após a restauração da dieta nutricional. Ao nascimento da ninhada, as progenitoras foram divididas nos seguintes grupos: Controle (C) com dieta a 23% de proteína ad libitum; Restrição Proteico-Calórica (RPC) com dieta a 8% de proteína e Restrição Calórica (RC) com dieta a 23% de proteína, em quantidades restritas de acordo com a ingestão do grupo RPC. Após o desmame, todos os filhotes foram separados das mães e receberam livre acesso a uma dieta padrão de laboratório contendo 23% de proteína, até 180 dias, quando os ratos foram eutanasiados. O fêmur foi excisado e as dimensões femorais macroscópicas foram medidas usando pontos anatômicos pré-estabelecidos. Após a morfometria macroscópica, os fêmures foram fixados em formol 10% (24h) e descalcificados por EDTA. Foram realizadas secções transversais de 10μm de espessura no terço médio diafisário dos espécimes, corados com HE e levados ao microscópio para análise qualitativa e histomorfometria da cortical óssea. Os resultados morfométricos macroscópicos mostraram que a maioria das medidas nos grupos de RC e RPC foram significativamente menores do que no grupo controle. As maiores reduções ocorrendo no grupo de RPC e com várias anormalidades histoarquiteturais, eg., diminuição da área cortical e aumento da área medular. Cortical com lacunas aumentadas significativamente nos grupos RC e RPC. Nossos resultados mostram que a restrição proteico-calórica durante a lactação leva a uma recuperação incompleta na idade adulta. O fêmur mostrou redução significativa na maior parte dos parâmetros macro e microscópicos nos dois grupos tratados, em particular o grupo RPC, quando comparado com o grupo C / The aim of this study was to evaluate the effects of maternal protein and energy restriction during lactation, analyzing on morphological dimensions whether there was catch-up growth through normative nutrition restored, as well as on mechanical axis of femur of the offspring at adulthood. At parturition, Wistar rat dams were randomly assigned to the following groups: 1) control group (C) - free access to a standard laboratory diet containing 23 % protein, 2) protein-energy restricted group (PER) - free access to an isoenergetic, protein-restricted diet containing 8 % protein, and 3) energy-restricted group (ER) – fed with restricted amounts of a standard laboratory diet. At weaning, all pups were separated of dams and received free access to a standard laboratory diet containing 23% protein until 180 days, when the rats were anesthetized and sacrificed. The dimensions of excised pup femur were measured directly using pre-established anatomical points. After macroscopic morphometry, the femurs were fixed in 10% formalin (24h) and decalcified by EDTA. Cross sections of 10μm thickness were made in the middle third (diaphyseal) of the specimens stained with HE and taken to the microscope for qualitative analysis and histomorphometry of cortical bone. Morphometric analysis of the femur (macroscopic) showed that most of the measurements in the ER and PER groups were significantly lower than in the control group, with the greatest reductions occurring in the PER group and several histoarchitectural abnormalities, e.g., decrease in cortical area and increased medullary area. Cortical bone with gaps increased significantly in ER and PER groups. Our results show that protein and energy restriction during lactation leads to an incomplete catch-up growth in adulthood. The femur showed significant reduction in most of the parameters in the two treated groups, particularly the PER group, when compared to the control group

(EN) GH/IGF-1 axis components (GH, growth hormone receptor (GH-R), IGF-1, IGF-1 receptor (IGF-1R), IGF-binding proteins (IGFBPs)) participate in the control of glucose metabolism, inflammatory processes as well as cell proliferation and differentiation, including adipocytes and monocytes. The aim of the present study was to evaluate the role of local mRNA expression of GH/IGF-1 axis components in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) in the development of insulin resistance and differences of adipose tissue mass in following groups of patients: obese females with and without type 2 diabetes mellitus and subjects with active untreated acromegaly. A total number of 66 subjects were included in the study: obese females without type 2 diabetes mellitus (OB), obese females with type 2 diabetes mellitus (T2DM), acromegalic patients (AC) and healthy lean control subjects (C). T2DM underwent 2 weeks of very-low- calorie diet (VLCD - energy content 2500 kJ/day). According to our results we suggest that decreased mRNA expression of IGF-1, IGF-1R, IGFBP-2 and IGFBP-3 in adipose tissue of T2DM subjects may contribute to changes of fat differentiation capacity and the increased IGF-1R mRNA expression in peripheral monocytes in these patients may play a role in the regulation of...

(AJ) Adipose tissue produces numerous adipokines, pro- and antiinflammatory cytokines and hormones which may influence the development of insulin resistance, type 2 diabetes mellitus and other comorbidities of the metabolic syndrome. The ability of adipose tissue to store lipids and thus protect other organs and tissues from ectopic lipid accumulation and development of insulin resistance (IR) is largely dependent on the adipogenic potential of preadipocytes. The amount and function of these cells may be the key factor in creating "healthy" adipose tissue or on the contrary "unhealthy" adipose tissue eventually leading to metabolic derangements. The regulation of the amount of body fat by converting preadipocytes into mature adipocytes may be crucial in the prevention and treatment of obesity and its comorbidities. One of the reasons for development of insulin resistance can be the inhibition of the differentiation process of preadipocytes into mature adipocytes with consequent ectopic lipid accumulation caused by the secretion of preadipocyte factor - 1 (Pref - 1). Pref - 1 has been discovered recently as a protein produced by preadipocytes but not by mature adipocytes. Pref - 1 is a member of the protein family sharing similarity with epidermal growth factors which regulate the differentiation of...